Integrin nanoclusters can bridge thin matrix fibres to form cell–matrix adhesions

Rishita Changede, Haogang Cai, Shalom J. Wind, Michael Sheetz

Research output: Contribution to journalArticle

Abstract

Integrin-mediated cell–matrix adhesions are key to sensing the geometry and rigidity of extracellular environments and influence vital cellular processes. In vivo, the extracellular matrix is composed of fibrous arrays. To understand the fibre geometries that are required for adhesion formation, we patterned nanolines of various line widths and arrangements in single, crossing or paired arrays with the integrin-binding peptide Arg-Gly-Asp. Single thin lines (width ≤30 nm) did not support cell spreading or formation of focal adhesions, despite the presence of a high density of Arg-Gly-Asp, but wide lines (>40 nm) did. Using super-resolution microscopy, we observed stable, dense integrin clusters formed on parallel (within 110 nm) or crossing thin lines (mimicking a matrix mesh) similar to those on continuous substrates. These dense clusters bridged the line pairs by recruiting activated but unliganded integrins, as verified by integrin mutants unable to bind ligands that coclustered with ligand-bound integrins when present in an active extended conformation. Thus, in a fibrous extracellular matrix mesh, stable integrin nanoclusters bridge between thin (≤30 nm) matrix fibres and bring about downstream consequences of cell motility and growth.

Original languageEnglish (US)
JournalNature Materials
DOIs
StateAccepted/In press - Jan 1 2019

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Nanoclusters
nanoclusters
Integrins
adhesion
Adhesion
fibers
Fibers
matrices
Linewidth
mesh
Ligands
ligands
locomotion
Geometry
geometry
cells
rigidity
Rigidity
Peptides
peptides

ASJC Scopus subject areas

  • Chemistry(all)
  • Materials Science(all)
  • Condensed Matter Physics
  • Mechanics of Materials
  • Mechanical Engineering

Cite this

Integrin nanoclusters can bridge thin matrix fibres to form cell–matrix adhesions. / Changede, Rishita; Cai, Haogang; Wind, Shalom J.; Sheetz, Michael.

In: Nature Materials, 01.01.2019.

Research output: Contribution to journalArticle

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